This invention relates to a blood control standard. More particularly, this invention is concerned with a stable blood control standard for the quality control of the measurement of blood pH and gases in the clinical laboratory and method of making the same.
Blood serum is a complex biological fluid containing various components of substantial physiological importance. In the normal or average healthy person the concentrations of these components fall within certain reasonably well-defined limits. When any of these components is found upon analysis to be outside of its normal range, a pathological condition may be indicated which requires medical attention.
The determination of blood gases, electrolytes and the acid-base balance is an important aspect of this blood analysis. Thus, abnormalities in pulmonary function may be indicated by the concentrations of oxygen and carbon dioxide in the blood. The importance of oxygen transport by the blood in respiration and the respiratory regulation of cation-anion balance is well known. By the process of homeostasis, the body tends to preserve a state of equilibrium which is manifested in three ways as applied to water and electrolyte metabolism:
1. Preservation of pH or acid-base balance. PA1 2. Preservation of ionic composition. PA1 3. Preservation of osmolality. PA1 pK is the log of the reciprocal of the dissociation constant of the bicarbonate system PA1 Hco.sub.3.sup.- is the true bicarbonate concentration in mmol/liter. PA1 H.sub.2 co.sub.3 is the carbonic acid concentration in mmol/liter
The buffer systems of the intra-and extra-cellular spaces preserve the pH within narrow limits. Of the various physiological buffers, only the bicarbonate system contains a component, carbon dioxide, which is volatile at body temperatures and, therefore, can be regulated by the lungs. Thus, an analysis of the bicarbonate buffer system enables a direct estimation of the respiratory acid-base balance. Dissolved carbon dioxide is present in plasma according to the following equation: EQU CO.sub.2 + H.sub.2 O .dbd. H.sub.2 CO.sub.3 .dbd. H.sup.+ + HCO.sub.3 --
carbon dioxide also is present in the red cells in the dissolved state, or combined with hemoglobin to form carbamino-CO.sub.2, or in a complex based on the action of the enzyme, carbonic anhydrase, which is present in the erythrocytes.
The interrelation between total CO.sub.2, bicarbonate, carbonic acid, pCO.sub.2 and pH in blood can be shown by the well-known Henderson-Hasselbalch equation: ##EQU1## in which pH is the pH measured in arterial blood
The values for pH, total CO.sub.2 and pCO.sub.2 can be determined experimentally and their mathematical relationships can then be illustrated by application of the Henderson-Hasselbalch equation.
Various instruments have been developed for the determination of the parameters which comprise the blood gases and acid-base balance. These instruments generally are capable of measuring blood pH, pCO.sub.2 and pO.sub.2. Illustrative of such instruments are those described in U.S. Pat. Nos. 3,658,478 and 3,652,843. Instruments of this type are commercially available from Instrumentation Laboratory Inc. as the IL 113 pH/Blood Gas Analyzer. Another such instrument is the Corning pH/Blood Gas Analyzer described in U.S. Pat. No. 3,763,422. Still another commercially available instrument for measuring blood pH, pO.sub.2 and pCO.sub.2 is the BMS3 Mk2 Blood Micro System and Digital Acid-Base Analyzer from The London Company, Radiometer A/S Instruments of the latter type are described in U.S. Pat. Nos. 3,654,445 and 3,874,850.
The use of the foregoing and other such instruments for the determination of blood gases in the clinical laboratory presents unique problems of quality control. The instruments must, of course, be properly calibrated in the first instance. Calibration of such instruments can be accomplished by metering standardized gases through the instrument or by application of a calibration fluid such as an aqueous bicarbonate solution as described, for example, in U.S. Pat. No. 3,681,255. However, calibration of the instrument is only one of the problems of blood gas clinical instrumentation. To ensure high quality patient care, the instrumentation system must be tested frequently and laboratory personnel must be promptly responsive to any system malfunction. For the latter purpose, control standards have been developed which can be applied to the instrument periodically at predetermined intervals to ensure adequate quality control. One such type of control standard is a freeze dried human serum which is reconstituted with a liquid diluent prior to use. Examples of this type of control standard are described in U.S. Pat. Nos. 3,466,249 and 3,629,412. These materials, however, are not fully useful for control purposes when the blood gas analysis includes determination of oxygen because the reconstituted serum does not contain the desired level of dissolved oxygen. Rather, they are adapted to control other biological values such as are determined on a Technicon SMA/12 Auto Analyzer.
Another such control standard contains blood which is reconstituted by the addition of a liquid containing fluoride and an iodoacetate or a fluoroacetate to stabilize the blood as disclosed in U.S. Pat. No. 3,859,049. However, this material similarily does not provide the desired levels of oxygen for the control of instruments which include the determination of blood oxygen. Although it is known that blood cells can be stabilized by various chemical fixatives as described in U.S. Pat. Nos. 3,574,137 and 3,640,896 or by thoroughly washing to separate from other blood constituents as described in U.S. Pat. No. 3,558,522, these materials are useful only for blood counting and similar such purposes and do not provide the necessary conditions for the control of blood pH and gases.
It is also known that blood cells can be stabilized for hemagglutination purposes or to serve as affinity absorbents for antigens or antibodies by rigorous treatment of the cells with aldehydes. Such treatment for use in diagnostic tests is described in U.S. Pat. Nos. 3,096,250, 3,426,123, 3,708,572, 3,714,345, and 3,925,541 and U.S. application Ser. No. 362,308, filed May 21, 1973, now U.S. Pat. No. 3,914,400. Again, these materials are useful for the disclosed diagnostic purposes but do not provide the herein-described conditions for control of blood pH and gases.
A recent patent has issued to Allan Louderback, namely, U.S. Pat. No. 3,973,913, the same inventor as herein. The patentee has disclosed a stable blood control standard and method for the quality control of the measurement of blood pH and gases in the clinical laboratory. While the technique includes a sealed receptacle containing specially treated red cells and a gaseous head space at least equal to about the volume of the red cells, no consideration in this prior art has been given to a way to obtain variable carbon monoxide levels with a whole blood product.
If one would just incorporate a quantity of carbon monoxide in the space above the blood in a glass vial, for instance, the results would be variable depending in how long one gassed the vials with carbon monoxide and then followed by gassing with variable oxygen, carbon dioxide and nitrogen in different concentrations as described in the abovementioned patent.